1. Field of the Invention
The present invention is directed to novel nutritional anti-nausea compositions, anti-emetic compositions and methods of using the same to provide relief from nausea and/or vomiting. The present compositions are also nonteratogenic and are therefore highly useful to pregnant women.
2. Description of the Related Art
Nausea and vomiting are two of the most common symptoms of illness and are also commonly experienced as side effects of numerous medical treatments. Both nausea and vomiting are also commonly experienced as a result of various external factors (e.g., travel) and during various conditions (e.g., pregnancy). Nausea and vomiting can occur individually or in conjunction with one another.
A common cause of nausea and vomiting is motion sickness. Motion sickness typically occurs when humans are subjected to long-lasting external movement or transportation accompanied by unusual movements such as shaking, waving, atmospheric changes (e.g., flying in an airplane), great acceleration, and uneven road conditions, etc. Motion sickness is not viewed as a disease but as a physiological symptom complex wherein the symptoms experienced, of which nausea and vomiting are common, depend on the individual in question. When the individual experiences motion sickness in a work environment, i.e., truck drivers, air pilots, air craft staff members and the like, the potential for a disadvantageous and dangerous condition result. Such individuals are often required to exhibit high level concentration and intellect, and the presence of motion sickness symptoms can severely detract from their ability to do so.
Though experienced by a more limited number of individuals, the nausea and vomiting associated with chemotherapy drugs and radiation treatment is especially problematic. Cancer treatment drugs such as Cisplatinum, Streptozotocin, Cytoxan, Nitrogen Mustard and Ara-C are known to cause severe nausea and vomiting as side effects. The reason that cancer drugs cause nausea and vomiting is still under investigation. It is believed that the drugs stimulate and irritate specific key areas in the brain which results in nausea and vomiting. Individuals undergoing cancer treatments and experiencing these side effects may feel discouragement beyond that which is directly related to their cancer. The inability to eat normally or to alleviate nausea can lead to increased patient depression. The Merck Manual, 1281-87 (16th Ed. 1992).
Postoperative nausea and vomiting is one of the most common side effects, estimated to be experienced by 20% to 30% of patients, after undergoing anesthetic and surgical procedures. Coates, A., "On the receiving end-patient perception of the side-effects of cancer chemotherapy", Eur J Cancer Clin Oncol, 19:203-208 (1983); See also, Cooper, et al., "The impact of cytotoxic chemotherapy-perspectives from patients, specialists and nurses", Eur J Cancer Clin Oncol, 28A(suppl 1):S36-S38 (1992). Research shows the occurrence of postoperative nausea and vomiting to be from 25% to 55% following inpatient surgery and from 8% to 47% for outpatient procedures. Id.; See also, Laszlo, J., "Nausea and vomiting as major complications of cancer chemotherapy", Drugs, 25(suppl 1):1-7 (1983); See also, Tortorice, et al., "Management of chemotherapy-induced nausea and vomiting", Pharmacotherapy, 10:129-145 (1990). When questioned prior to surgery, patients are often more concerned about post-operative nausea and vomiting than post-operative pain, since they perceive that the nausea and vomiting will be more debilitating. Tonato, et al., "Methodology of antiemetic trials: a review", Ann Oncol, 2:107-114 (1991); See also, Fauser, et al., "Therapeutic equivalence of single oral doses of dolasetron mesilate and multiple doses of ondansetron for the prevention of emesis after moderately emetogenic chemotherapy," Eur J Cancer, 32A(9):1523-1529 (1996).
Nausea and vomiting are also both common in early pregnancy. Cases can range in degree from mild to severe, and symptoms usually begin soon after the first missed period. Morning sickness, i.e., nausea and vomiting experienced during the first and second trimesters of pregnancy, is experienced by approximately half of all pregnant women, however it is particularly common in cases of multiple pregnancy and hydatidiform mole. Kousen, M., "Treatment of nausea and vomiting in pregnancy", Am Fam Physician, 48:1279 (1993).
Hyperemesis gravidarum, i.e., persistent nausea and vomiting during pregnancy, can lead to a reduction in fluid and electrolyte levels, as well as a jeopardized nutritional status if the condition is not treated. The condition is characterized by prolonged and severe nausea and vomiting, dehydration, ketosis, and body weight loss. Other complications may include hyponatraemia, hypokalaemia, a low serum level, metabolic hypochloraemic alkalosis, ketonuria, liver function test abnormalities, abnormal thyroid function tests, and suppressed thyroid-stimulating hormone levels. Nelson-Piercy, C., "Treatment of nausea and vomiting in pregnancy. When should it be treated and what can be safely taken?", Drug Saf, 19(2):155-64 (1998).
Nausea and vomiting can also be brought on by a variety of other causes such as reactions to certain types of odors or visual stimuli, psychological perceptions, allergic reactions, drug interactions and the like. Whatever the cause, the presence of a nauseated and/or emetic condition in an individual can be debilitating for the period during which it is experienced, and therefore numerous antiemetic and antinausea compositions and methods have been described.
Many generalized nausea and vomiting treatment compositions have been described. For example, Tyers et al., U.S. Pat. No. 5,578,628, describe tetrahydrocarbazolone derivatives which may be used for the prevention and treatment of nausea.
Lovgren et al., U.S. Pat. No. 4,786,505, describe a pharmaceutical preparation containing omeprazole for oral use and a method of affecting gastric acid secretion and providing gastrointestinal cytoprotective effect when using them.
Lovgren, U.S. Pat. No. 4,853,230, describes an easily water soluble pharmaceutical preparation containing an acid labile compound together with and alkaline reacting compound for the treatment of gastrointestinal diseases.
Bodo et al., U.S. Pat. No. 4,925,878, describe a composition especially suited for the treatment of the nausea and vomiting symptoms associated with motion sickness.
Numerous drugs have been developed for the treatment of chemotherapy-induced vomiting and nausea. Zofran.RTM., a prescription antiemetic drug containing ondansetron as the active component, is a highly selective antagonist of serotonin receptors. Clinically accepted for use in treating cancer chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and radiotherapy induced nausea and vomiting, this medication is not accepted for use in the treatment of motion-sickness or for prescription to pregnant or nursing women. Drug Information for the Health Care Professional, 2179 (17.sup.th Ed., 1997).
Kytril.RTM., another prescription antiemetic, containing the active component granisetron, also works as a highly specific antagonist of serotonin receptors. Clinically, Kytril.RTM. is only accepted for use in treating cancer chemotherapy-induced nausea and vomiting and has not been proven safe for prescription to pregnant or nursing women. Id. at 1532.
In relation to the treatment of nausea and/or vomiting in pregnant women, different approaches have been attempted in order to avoid teratogenicity or at least reduce the risk of birth defects commonly associated with certain drugs for treating nausea and vomiting.
Studies have shown that certain vitamins may reduce nausea and/or vomiting. Administration of pyridoxine was shown to be effective in relieving the severity of nausea in early pregnancy without being teratogenic. Vutyavanich, et al., "Pyridoxine for nausea and vomiting in pregnancy:
a randomized, double-blind, placebo-controlled trial", Am J Obstet Gynecol, 173:881-4 (1995).
Further, it has been shown that the nausea and vomiting of pregnancy can be mitigated if the patient eats small portions of food at frequent intervals, increases the amount of carbohydrates, decreases the amount of fat, and avoids "bothersome food odors." Kousen, M., "Treatment of nausea and vomiting in pregnancy", Am Fam Physician, 48(7):1279-84 (1993).
Nutritional compositions for general improvement of health have been described in the related art. Green, U.S. Pat. No. 4,806,345, describes a health food composition which is comprised of B complex vitamins, i.e., thiamine, pyridoxine, riboflavin, and cyanocobalamin, an emulsifying agent, flavoring agent, a preservative agent and optionally an antacid such as calcium carbonate and/or an analgesic such as acetaminophen.
Meshansho, et al., U.S. Pat. No. 4,994,283, describe a nutritional composition comprised of iron compounds and calcium compounds in combination with citrates or tartrates, ascorbates, and, optionally, fructose.
Clark, U.S. Pat. No. 4,738,856, describes a yet another nutritional composition in the form of a beverage solution, which comprises calcium, magnesium, potassium, a sweetener agent and a stabilizer. The invention is specifically designed to have a reducing effect on conditions such as high blood pressure and high blood alcohol content.
It is generally accepted that it is of significant advantage under certain circumstances to both patients, physicians and nonpatients that medications and/or nutritional compositions be formulated so that they may be administered in a minimal number of daily doses from which the medication and/or nutritional composition is uniformly released over a desired, extended period of time. Such delivery methods are particularly useful for the sake of convenience when repeat dosing is necessary to bring about a desired therapeutic or physiological effect. Such delivery systems have been described.
Ayer et al., U.S. Pat. No. 4,948,592, describe a pulsed drug delivery system comprising an immediately available dose of a beneficial drug followed by a timed delayed dose of the drug, or simply a timed delayed dose of the drug.
Guley et al., U.S. Pat. No. 4,309,405, describe a sustained release tablet wherein the active drug in a core structure of the tablet surrounded by a water soluble polymer such hydroxypropylmethylcellulose or hydroxypropylcellulose and a water insoluble polymer such as ethylcellulose.
Another form of drug delivery which has been accepted as useful to both patients, physicians and nonpatients is the chewable tablet dosage form. This type of dosing finds particular applicability in persons who have difficulty swallowing tablet-type forms of medications and/or nutritional compositions or when the substance contained within the tablet is most beneficial when delivered immediately, such as with antacid formulations. Chewable tablets forms have been described in the art.
Weckenamnn et al., U.S. Pat. No. 5,648,092, describe pharmaceutical compositions in the form of pleasant tasting chewable tablets containing sulcralfate, which is employed for the treatment of duodenal ulcers, gastric ulcers and reflux esophagitis.
While numerous antiemetic compositions and methods exist, these compositions often produce numerous and undesired patient side-effects. These formulation have the result of placing the patient in the position of choosing between the condition she or he seeks to alleviate and the side effect of the therapy. Further, these formulations do not utilize vitamins and minerals as active components, and therefore have no direct positive impact on the patient's nutritional status. Thus, it is desirable to have effective antiemetic formulations which have few side effects and are nutritionally beneficial to the taker.
The disclosed antiemetic compositions are deficient in various other respects. Primarily, none have undergone extensive clinical studies on humans with regards to teratogenicity, and thus are not recommended for ingestion by pregnant women except for in the most extreme of situations. Even the above discussed references which recognize the potential for teratogenicity, and thus seek to provide for alternative methods of treatment, do not specifically disclose distinct nutritional formulations for treating nausea and vomiting. Further these references do not provide any guidance with regard to formulating nutritional compositions for treating nausea and vomiting.
Therefore, it is desirable to have formulations available which are effective in providing relief to nausea and vomiting arising from various causes. Moreover, there is a particular need for formulations which simultaneously relieve nausea and/or vomiting and provide a higher degree of patient compliance and are available at minimal cost. Additionally, there remains a need for specific nutritional formulations which have an antiemetic effect, are nonteratogenic, and also support good health. It is also particularly desirable to have formulations available which minimize the need to take medications and which are suitable to be taken by individuals who seek to limit their use of medications. Thus, there is a general overall need for a fundamentally new, safe, effective and comprehensive approach to addressing the treatment of nausea and vomiting arising from various causes.